P53-dependent miRNAs mediate nitric oxide-induced apoptosis in colonic carcinogenesis

Li, Weiwei; Han, Wenxiao; Ma, Yiming; Cui, Liang; Tian, Yantao; Zhou, Zhixiang; Wang, Hongying

doi:10.1016/j.freeradbiomed.2015.04.016

Cited by 24 publications

(10 citation statements)

References 35 publications

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“…Our research demonstrated that SA could inhibit the proliferation and induce the apoptosis of hepatoma cell line in a time-and dose-dependent manner, which implies a potential application of SA as an anti-cancer agent. Nitric oxide (NO) in cancer cells was produced at submicromolar levels to activate signaling pathways leading to evasion of apoptosis on the one hand and promotion of cell proliferation, migration, and metastatic invasion on the other (Tan et al 2013;Li et al 2015). A few reports (Karmohapatra et al 2007) have demonstrated that aspirin could activate nitric oxide synthase from human blood platelets.…”

Section: Discussionmentioning

confidence: 99%

The apoptotic inducible effects of salicylic acid on hepatoma cell line: relationship with nitric oxide signaling

Liu

Wang

et al. 2017

J. Cell Commun. Signal.

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Clinical and experimental data suggest that salicylic acid (SA) is tumor preventive and NO has a multitude of effects on tumor biology. Therefore, firstly, the aim of our study is to explore the important role of SA in apoptotic induction of liver cancer cells. Secondly, we investigate whether SA mediates the anti-tumor effects by NO signaling pathway. The liver cancer cell line was treated with different concentrations of SA. Cell proliferation was tested using MTS assay and cell apoptosis was assessed by flow cytometry. NO content and NOS activities were measured by biochemical assay. The anti- or pro-apoptotic regulator gene expressions were analyzed by real-time PCR. Our data illustrated that high concentration of SA significantly inhibited liver cancer cell proliferation accompanied by apoptosis induction. In addition, SA led to the release of NO and the increase of NOS activities in above process. Importantly, SA up-regulated a series of apoptosis-related gene expression and reduced the mRNA level of HMGB1. Meanwhile, we also found that NOS inhibitor L-NAME and NO scavenger cPTIO attenuated the above SA-induced effects. Thus, we provided the evidence that SA exerted anti-tumor effects in liver cancer cell in part mediated by the NO pathway.

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Section: Discussionmentioning

confidence: 99%

The apoptotic inducible effects of salicylic acid on hepatoma cell line: relationship with nitric oxide signaling

Liu

Wang

et al. 2017

J. Cell Commun. Signal.

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“…However, cells with p53 mutations can evade this apoptotic mechanism. Therefore, elevated NO concentration in tumors selectively kills healthy cells and allows cancer cells to survive, thereby contributing to tumor progression [27]. A correlative study in oral squamous cell carcinoma patients made a similar observation, where tumors in advanced stages of the disease showed higher NOS expression and lower p53 expression [28].…”

Section: No: Modulator Of the Tmementioning

confidence: 98%

Nitric Oxide: The Forgotten Child of Tumor Metabolism

2017

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Nitric oxide (NO) is a signaling molecule with pleiotropic physiological roles in normal cells and pathophysiological roles in cancer. NO synthetase expression and NO synthesis are linked to altered metabolism, neoplasticity, invasiveness, chemoresistance, immune evasion, and ultimately to poor prognosis of cancer patients. Exogenous NO in the microenvironment facilitates paracrine signaling, mediates immune responses, and triggers angiogenesis. NO regulates posttranslational protein modifications, S-nitrosation, and genome-wide epigenetic modifications that can have both tumor-promoting and tumor-suppressing effects. We review mechanisms that link NO to cancer hallmarks, with a perspective of co-targeting NO metabolism with first-line therapies for improved outcome. We highlight the need for quantitative flux analysis to study NO in tumors.

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“…After exposure to sirolimus, miR-34b was significantly up-regulated. MiR-34, a tumor suppressor miRNA family, is considered to be a critical mediator of p53 function [12][13][14] . Several studies have demonstrated its role in resistance or sensitization to anticancer drugs [15,16] .…”

Section: Introductionmentioning

confidence: 99%

Sirolimus induces apoptosis and reverses multidrug resistance in human osteosarcoma cells in vitro via increasing microRNA-34b expression

et al. 2016

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Aim: Multi-drug resistance poses a critical bottleneck in chemotherapy. given the up-regulation of mToR pathway in many chemoresistant cancers, we examined whether sirolimus (rapamycin), a first generation mTOR inhibitor, might induce human osteosarcoma (os) cell apoptosis and increase the sensitivity of os cells to anticancer drugs in vitro. Methods: human os cell line Mg63/aDM was treated with sirolimus alone or in combination with doxorubicin (aDM), gemcitabine (GEM) or methotrexate (MTX). Cell proliferation and apoptosis were detected using CCK-8 assay and flow cytometry, respectively. MiRnas in the cells were analyzed with miRna microarray. The targets of miR-34b were determined based on Targetscan analysis and luciferase reporter assays. The expression of relevant mRna and proteins was measured using qRT-PCR and Western blotting. MiR-34, PaK1 and aBCB1 levels in 40 tissue samples of os patients were analyzed using qRT-PCR and in situ hybridization assays. Results: Sirolimus (1−100 nmol/L) dose-dependently suppressed the cell proliferation (IC 50 =23.97 nmol/L) and induced apoptosis. Sirolimus (10 nmol/L) significantly sensitized the cells to anticancer drugs, leading to decreased IC 50 values of aDM, geM and MTX (from 25.48, 621.41 and 21.72 μmol/L to 4.93, 73.92 and 6.77 μmol/L, respectively). Treatment of with sirolimus increased miR-34b levels by a factor of 7.5 in the cells. upregulation of miR-34b also induced apoptosis and increased the sensitivity of the cells to the anticancer drugs, whereas transfection with miR-34b-aMo, an inhibitor of miR-34b, reversed the anti-proliferation effect of sirolimus. Two key regulators of cell cycle, apoptosis and multiple drug resistance, PaK1 and aBCB1, were demonstrated to be the direct targets of miR-34b. In 40 tissue samples of OS patients, significantly higher miR-34 ISH score and lower PAK5 and ABCB1 scores were detected in the chemo-sensitive group. Conclusion: sirolimus increases the sensitivity of human os cells to anticancer drugs in vitro by up-regulating miR-34b interacting with PaK1 and aBCB1. a low miR-34 level is an indicator of poor prognosis in os patients.

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P53-dependent miRNAs mediate nitric oxide-induced apoptosis in colonic carcinogenesis

Cited by 24 publications

References 35 publications

The apoptotic inducible effects of salicylic acid on hepatoma cell line: relationship with nitric oxide signaling

The apoptotic inducible effects of salicylic acid on hepatoma cell line: relationship with nitric oxide signaling

Nitric Oxide: The Forgotten Child of Tumor Metabolism

Sirolimus induces apoptosis and reverses multidrug resistance in human osteosarcoma cells in vitro via increasing microRNA-34b expression

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